Methanol → 2-[5-(3-{[5-(4-ethyl-1,3-thiazol-2-yl)-2-pyridinyl]oxy}propoxy)-1H-indol-1-yl]propanoic acid

HRID 734431Notes

Reaction equation

HRID 734431 reaction equation
[OH-].[Li+].[CH2:3]([C:5]1[N:6]=[C:7]([C:10]2[CH:11]=[CH:12][C:13]([O:16][CH2:17][CH2:18][CH2:19][O:20][C:21]3[CH:22]=[C:23]4[C:27](=[CH:28][CH:29]=3)[N:26]([CH:30]([CH3:35])[C:31]([O:33]C)=[O:32])[CH:25]=[CH:24]4)=[N:14][CH:15]=2)[S:8][CH:9]=1)[CH3:4].CO.O>C1COCC1>[CH2:3]([C:5]1[N:6]=[C:7]([C:10]2[CH:11]=[CH:12][C:13]([O:16][CH2:17][CH2:18][CH2:19][O:20][C:21]3[CH:22]=[C:23]4[C:27](=[CH:28][CH:29]=3)[N:26]([CH:30]([CH3:35])[C:31]([OH:33])=[O:32])[CH:25]=[CH:24]4)=[N:14][CH:15]=2)[S:8][CH:9]=1)[CH3:4]

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 3939Lithium HydroxideHCID 57845392methyl 2-[5-(3-{[5-(4-ethyl-1,3-thiazol-2-yl)-2-pyridinyl]oxy}propoxy)-1H-indol-1-yl]propanoate

Product 1

HCID 115397032-[5-(3-{[5-(4-ethyl-1,3-thiazol-2-yl)-2-pyridinyl]oxy}propoxy)-1H-indol-1-yl]propanoic acidYield 83.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Lithium hydroxide (0.05 g, 2.15 mmol) was added to a solution of methyl 2-[5-(3-{[5-(4-ethyl-1,3-thiazol-2-yl)-2-pyridinyl]oxy}propoxy)-1H-indol-1-yl]propanoate (Example 69, 0.1 g, 0.21 mmol) in a mixture of THF (2 mL), methanol (2 mL), and water (1 mL). The reaction mixture was stirred at rt for 18 h and then concentrated under reduced pressure. The residue was diluted with water and acidified with 5% H3PO4. The aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried over Na2SO4, filtered, and concentrated to give the title compound as a solid (0.079 g, 82%). 1H NMR (400 MHz, CD2Cl2) δ 8.45 (dd, 1H), 7.94 (dd, 1H), 7.08-6.62 (m, 6H), 6.22 (d, 1H), 4.94 (qt, 1H), 4.37 (t, 2H), 4.00 (t, 2H), 2.66 (qt, 2H), 2.31-2.07 (m, 2H), 1.60 (d, 3H), 1.15 (t, 3H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionThe residue was diluted with water
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. dry with materialThe combined organic extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-319dc376a1684e70b6a9f0ca573ac1c3
Source dataset
uspto-grants-2009_09
Patent number
US07592361B2

Reaction notes

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